In the past few months, as AstraZeneca got its COVID-19 vaccine approved in Britain, Canada and Europe, it has contended with a growing list of concerns about its research and marketing techniques as well as deepening worries about whether the vaccine is causing blood clots, including obstructions that prevent blood from draining from the brain (known as cerebral venous sinus thrombosis), which killed at least nine people in Germany shortly after they received the AstraZeneca vaccine.
On Monday, Canada’s National Advisory Committee on Immunizations (NACI) altered its guidance regarding the AstraZeneca COVID-19 vaccine and recommended a pause in giving it to adults under 55 years of age until more investigations could occur into a possible relationship between the vaccine and blood clots.
Didn’t the European Medicines Agency already review that blood clot concern and say the vaccine was safe?
Earlier in March, as reports of blood clots were being flagged in the surveillance systems that monitor any possible post-vaccination side effects, more than 20 European countries temporarily stopped using the AstraZeneca vaccine. At that point, there were 37 reports of blood clots among the more than 17 million people who received doses in Europe and Britain.
On March 18, the European Medicines Agency (EMA) stated that the AstraZeneca COVID-19 vaccine “is not associated with an increase in the overall risk of blood clots.” Still, while the EMA committee conducting the preliminary review was of the opinion that the vaccine’s proven efficacy in preventing hospitalization and death from COVID-19 outweighed the extremely small likelihood of developing two rare blood clotting disorders, it also cautioned that the vaccine may be associated with very rare cases of blood clots associated with low levels of blood platelets.
What changed since that EMA decision and what is VIPIT?
Research into the clotting issue didn’t stop, especially into that unusual combination of people having widespread blood clots and low platelet counts, which resembles “a rare side effect of the blood thinner heparin called heparin-induced thrombocytopenia,” Science magazine reported.
Clotting specialist Andreas Greinacher named that combination of symptoms “vaccine-induced prothrombotic immune thrombocytopenia,” or VIPIT. And, as Science reports, though other researchers weren’t sure of Greinacher’s explanation, they were convinced that the vaccine was causing rare symptoms. A hematologist in the United States told The Atlantic that while he wasn’t yet convinced by the “vaccine-induced” part of the VIPIT name, he did think “these cases raise concern that this vaccine is potentially life-threatening in a small subset of patients.”
How common is VIPIT among those who have received the AstraZeneca vaccine and why are those clots concerning enough for NACI to change its recommendation?
The Ontario COVID-19 Science Advisory Table offers a lay summary: “These blood clots have two important features: they occur four to 20 days after vaccination, and they are associated with low platelets (tiny blood cells that help form blood clots to stop bleeding).”
Research is still very early. Scientists had found at least 13 people who had received the AstraZeneca vaccine and who had both blood clots as well as low platelet counts before the EMA decision, according to Science magazine. And that later research, led by Greinacher, looked at nine people who exhibited blood clotting events after vaccination (seven had cerebral venous sinus thrombosis (CVST); another had CVST plus another vein thrombosis; the ninth had a pulmonary embolism; four of them died), and examined the blood samples that were available for four of them.
Most of the cases of VIPIT in Europe involve women under 55 years of age, though that may be the result of vaccines being given to more women than men. Right now, according to NACI, “the case fatality of VIPIT is approximately 40 percent,” though that the rate may fall with more awareness of the potential side effect and earlier treatment.
While scientists need to conduct more research into establishing whether there is a definite link between VIPIT and the AstraZeneca vaccine, NACI felt there was enough new data that it wanted to revise its recommendation, which it did on Monday.
To date, no cases of VIPIT have been reported in Canada. As of now, “VIPIT seems to be rare, occurring in anywhere from 1 in every 125,000 to 1 in 1 million people,” the Science Table stated in its March 26 guidance, though those statistics are being constantly updated.
On Monday, the Paul-Ehrlich-Institut released more surveillance data for Germany: of around 2.7 million people given the AstraZeneca vaccine, there have been 31 cases of CVST (29 were women), with nine deaths. How many of those cases of cerebral blood clots also have low platelet counts isn’t yet known.
What role does Health Canada play, given it has approved AstraZeneca for use?
On Tuesday, March 30, Dr. Theresa Tam, Canada’s chief public health officer, explained that Health Canada, as the regulator of vaccines, “triggered a signal to the manufacturer to say we need more data, we need it to be broken down by age and sex, to look for this more serious and rare side effect that is being seen following immunization, even though we haven’t seen it yet in Canada.”
“While the data is being gathered,” Tam continued, “we amassed experts from Canada but also had experts from Germany provide what their first-hand interpretation of what this clotting with low platelets entity is like and some of the underlying scientific explanations.”
At that point, NACI said that while it was waiting for more information, it had seen enough new science from Europe to “take the precautionary approach,” Tam continued. “And given the data that we’ve seen where most of these rare cases occur in the under-55s, that’s the recommendation they have provided to pause offering AstraZeneca vaccine for this age group, for now.”
After NACI made this new recommendation, all the chief medical officers in Canada met virtually, were briefed on the new information and recommendations and “made a unified position to take this precautionary approach,” Tam explained, “to keep Canadians as safe as possible while offering a safe and effective vaccine.”
Health Canada is conducting a “full risk assessment” of the AstraZeneca vaccine, Dr. Tam explained.
Why weren’t these possible health issues detected earlier?
“The advice on any medication or vaccine can evolve over time, and I think Canadians should be reassured that we have systems in place to detect safety signals and then analyze them,” Dr. Tam explained on Tuesday. “Every medication or vaccine can come with rare side effects which will not be picked up until many millions of people receive the vaccine. The initial clinical trial, with tens of thousands, will not pick up rare events. So I think the important thing to emphasize to everyone is that we have systems and checks and balances in place.”
How many Canadians under 55 have gotten the vaccine?
That’s not clear, though the number is likely quite low. As of now, only around 310,000 doses of AstraZeneca have been distributed for use in Canada, Tam says, with most provinces, including Ontario, giving them to people 60 and older.
What happens to those Canadians under 55 who have received a shot of AstraZeneca?
Federal officials are working on that advice right now, but Dr. Howard Njoo, Canada’s deputy chief medical officer of health, points out that, as there are up to 16 weeks between doses, there is time to figure out a next step before that issue becomes pressing. One possible solution may be to mix-and-match the first AstraZeneca dose with a second dose of mRNA vaccine from Pfizer or Moderna. There is a study being conducted in Britain right now regarding such a strategy.
Wait a sec, let’s back up: Initially, those who are 65 years and older were barred from getting the AstraZeneca vaccine. Then it was all adults. Now it’s OK for just those 55 and older. What’s going on?
Your confusion is justified. This new NACI recommendation is its third for the AstraZeneca vaccine in less than a month.
On March 1, shortly after Health Canada approved the vaccine for use, NACI recommended it only be given to those between 18 and 64 years of age. There were concerns as to the vaccine’s efficacy for seniors because its phase three trials in Britain, Brazil and South Africa hadn’t included many from the 65-plus cohort.
On March 16, NACI changed its recommendation to all adults, 18 and older, including the 65-plus age group, based on real world studies, especially in Britain, which showed the vaccine to be effective for seniors, especially against severe COVID-19 and hospitalizations.
Then on March 29, came its “pause” recommendation for those younger than 55.
This seems to be the latest in a long line of concerns for the AstraZeneca vaccine, right?
Last November, there were reports that some volunteers in AstraZeneca’s phase three trials had accidentally been given only half of the recommended first dose. This complicated the analysis of the data, especially when it was revealed that the efficacy for those who received the mistaken dosing appeared to be much stronger than those who received two normal-strength doses.
Researchers also questioned how AstraZeneca mixed results from several studies, which were conducted differently, into one overall efficacy result.
Then there is AstraZeneca’s fight with the European Union. The EU was furious when, in late January, AstraZeneca suddenly announced it was cutting its delivery of doses to the EU by 60 percent in the first quarter of the year, as it struggled with manufacturing and supply problems.
And in the United States, where AstraZeneca went through separate phase three trials and is still not approved, there was even more controversy when, on March 22, the company announced an efficacy of 79 percent. Late that same day, the National Institutes of Health issued a rare public rebuke, saying that AstraZeneca “may have included outdated information from that trial, which may have provided an incomplete view of the efficacy data.” On March 23, AstraZeneca tried again with a new press release claiming a 76 percent efficacy.
On March 25, AstraZeneca changed its vaccine’s name from “COVID-19 Vaccine AstraZeneca” to Vaxzevria, according to the European Medicines Agency. Whether adopting a more formal name will help its image is uncertain.
At same time, it’s still an effective vaccine against COVID-19?
Yes, of that there is no doubt. It and the Pfizer mRNA vaccine are the two main COVID-19 vaccines used in Britain. Already, more than 30 million people in the United Kingdom have received at least one dose, and the result has been a steady decrease in cases, hospitalizations and deaths, even as the B.1.1.7 variant of concern became the dominant strain of the virus.
What do I do if I’m offered AstraZeneca?
That’s a personal decision. Experts consistently say that the best vaccine is the one in an arm, but that doesn’t stop the worry.
As Ontario’s Science Table explains, Health Canada has “stated that the benefits in protecting Canadians from COVID-19 continue to outweigh the risks and encourage Canadians to get immunized with any of the COVID-19 vaccines that are authorized in Canada when they are eligible. Keep in mind that COVID-19 has killed [more than 22,000] Canadians so far, that about 1 in 100 Canadians who get COVID-19 end up needing intensive care, and that 1 in 5 Canadians who are hospitalized with COVID-19 develop blood clots. Currently Canada is experiencing a third wave of COVID-19. VIPIT is very rare, while the AstraZeneca vaccine has proven effective at reducing severe illness from COVID-19.”
What symptoms do I need to look out for if I get the AstraZeneca vaccine?
In general, you should always look out for any unusual or severe symptoms after receiving any vaccine, and contact a health care professional or an emergency department if any develop.
Health Canada has issued a warning: “Seek immediate medical attention if you develop shortness of breath, chest pain, leg swelling, or persistent abdominal pain following vaccination. Also, seek immediate medical attention if you experience after a few days severe or persistent headaches or blurred vision, or experience skin bruising or pinpoint round spots beyond the site of vaccination which appears after a few days.”
That vigilance is for between four and 20 days after the vaccination, according to NACI and Ontario’s Science Table.
If the AstraZeneca vaccine remains available only for those 55 and older—or is further restricted or even withdrawn—how does that affect our vaccination program?
While Canada has ordered 22 million doses of AstraZeneca vaccine, the country is also receiving tens of millions of doses of other approved vaccines, including from Moderna (up to 44 million), Pfizer (up to 40 million) and Johnson & Johnson (up to 38 million).
In the near term, Canada expects to receive 12.3 million Moderna doses and 17.8 Pfizer doses between April and June.
So, if the AstraZeneca vaccine continues to be only for those 55 and older, or is removed altogether, there are enough other suppliers to ensure our vaccination rollout continues on pace for all eligible Canadians to be vaccinated by September.
What about the rest of the world?
If the scientific community is able to definitively link the blood clot issue to the AstraZeneca vaccine and deems it a serious enough risk to justify rethinking its use, that could be a huge blow to immunization efforts around the world, as it’s a key vaccine for the World Health Organization’s plan. Yet, at the same time, it’s best to discover any potential concerns now, before the rollout to countries lacking the robust surveillance systems of Europe and North America.